medgenМедицинская генетикаMedical Genetics2073-7998Publishing House «Genius Media» LLC10.1234/XXXX-XXXX-2016-9-17-28medgen-169Research ArticleОРИГИНАЛЬНЫЕ ИССЛЕДОВАНИЯORIGINAL RESEARCHМолекулярно-генетическая и биохимическая характеристика изолированной метилмалоновой ацидурии у российских пациентовMolecular and biochemical characteristics of the isolated methylmalonic aciduria in Russian patientsКуркинаМ. В.KurkinaM. V.labnbo@yandex.ruБайдаковаГ. В.BaydakovaG. V.noemail@neicon.ruЗахароваЕ. Ю.ZakharovaE. Y.noemail@neicon.ruФедеральное государственное бюджетное научное учреждение «Медико-генетический Научный Центр»РоссияFSBI «Research Centre for Medical Genetics»Russian Federation2016131020161591728Copyright © Куркина М.В., Байдакова Г.В., Захарова Е.Ю., 20162016Куркина М.В., Байдакова Г.В., Захарова Е.Ю.Kurkina M.V., Baydakova G.V., Zakharova E.Y.Данная работа распространяется под лицензией Creative Commons Attribution 4.0.This work is licensed under a Creative Commons Attribution 4.0 License.https://www.medgen-journal.ru/jour/article/view/169

После расшифровки генетических основ метилмалоновой ацидурии (ММА) стало понятно, что это обширная группа наследственных болезней, которую объединяет повышение уровня метилмалоновой кислоты (ММК) в биологических жидкостях. С биохимической точки зрения выделят две группы ММА: изолированную и комбинированную. Первая объединяет заболевания, связанные с мутациями в генах метилмалонил-КоА мутазы, метилмалонил-КоА эпимеразы и болезни, обусловленные нарушением метаболизма витамина B12. Во вторую группу включают комбинированную ММА с гомоцистеинемией/гомоцистинурией, обусловленную мутациями в нескольких генах, участвующих в биогенезе митохондрий. Своевременная диагностика этих заболевания крайне важна, поскольку разработаны подходы к диетотерапии ММА, а применение гидроксикобаламина для B12-чувствительных форм позволяет практически нивелировать все клинические проявления болезни. Немаловажным фактором, затрудняющим ДНК-диагностику многих наследственных заболеваний, является выявление изменений нуклеотидной последовательности, трактовка патогенетического значения которых затруднена. В данной работе нами проведен анализ биохимического фенотипа у 31 пациента с изолированной ММА, ДНК-диагностика проведена 18 пациентам. У 13 больных обнаружены мутации в гене MUT и у 3 пациентов - в гене ММАА , у 2 пациентов проведен анализ гена ММАА и мутаций выявлено не было, планируется провести исследование гена MMAB . Мутации, выявленные в гене MUT , впервые были проанализированы с применением нескольких программ по предсказанию патогенности мутаций.

Methylmalonic aciduria (ММА) - genetically heterogeneous group of hereditary diseases, which characterized by increase of methylmalonic acid (MA) in biological fluids. Biochemically ММА is divided into two groups: isolated and combined. The first one includes diseases associated with mutations in the genes of methylmalonyl-CoA mutase, methylmalonyl-CoA epimerase and diseases caused by disturbance of vitamin B12 metabolism. The second one includes combined MMA with homocysteinemia/homocystinuria caused by mutations in several genes involved in mitochondrial biogenesis. Early diagnosis of the disease is extremely important, since developed approaches to diet therapy of MMA, and the using of hydroxocobalamin for B12-responsive forms allows virtually neutralize all the clinical manifestations of the disease. One of the difficulties of DNA diagnostics is verification of variants in the genes, which pathogenicity is not clear enough. In this research, we studied a biochemical phenotype analysis of 31 patients with isolated MMA. DNA diagnostics was carried out in 18 patients. Mutations in the MUT gene were found in 13 patients. Mutations in the MMAA gene were found in 3 patients. In 2 patients mutations were not found in the MMAA gene. It is planned to study MMAB gene. At first time in our research were found mutations in the MUT gene which were analyzed with programs for the prediction of pathogenicity.

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The authors declare that there are no conflicts of interest present.